The long-term objectives of the project are to determine the mechanisms responsible for ethanol-induced cardiomyopathies during fetal development and to devise treatments which will reverse or prevent the occurrence of alcohol-related myopathies. The specific aims are designed to investigate possible mechanisms involved in the production of mitochondrial abnormalities in ethanol-exposed muscle. Transcriptional regulation will be investigated by determining the relative levels of nuclear and mitochondrial mRNAs encoding different subunits of cytochrome c oxidase (COX). Polyclonal antibodies will be raised against nuclear and mitochondrial COX subunits and used to investigate the translational regulation of COX by measuring the steady state levels and synthesis rats of COX subunits. Techniques to identify the subcellular distribution of COX mRNAs and subunits will be developed in order to investigate their localization in abnormal mitochondria. A model employing the chronic stimulation of skeletal muscle will be developed to determine if ethanol exposure disrupts the normal events of mitochondrial biogenesis in trained muscle.